Apelin and its receptor control heart field formation during zebrafish gastrulation

Dev Cell. 2007 Mar;12(3):391-402. doi: 10.1016/j.devcel.2007.01.011.


The vertebrate heart arises during gastrulation as cardiac precursors converge from the lateral plate mesoderm territories toward the embryonic midline and extend rostrally to form bilateral heart fields. G protein-coupled receptors (GPCRs) mediate functions of the nervous and immune systems; however, their roles in gastrulation remain largely unexplored. Here, we show that the zebrafish homologs of the Agtrl1b receptor and its ligand, Apelin, implicated in physiology and angiogenesis, control heart field formation. Zebrafish gastrulae express agtrl1b in the lateral plate mesoderm, while apelin expression is confined to the midline. Reduced or excess Agtrl1b or Apelin function caused deficiency of cardiac precursors and, subsequently, the heart. In Apelin-deficient gastrulae, the cardiac precursors converged inefficiently to the heart fields and showed ectopic distribution, whereas cardiac precursors overexpressing Apelin exhibited abnormal morphology and rostral migration. Our results implicate GPCR signaling in movements of discrete cell populations that establish organ rudiments during vertebrate gastrulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apelin Receptors
  • Body Patterning / physiology
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Embryonic Development / physiology
  • Gastrula / cytology
  • Gastrula / metabolism*
  • Gene Expression Regulation, Developmental / physiology
  • Heart / embryology*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mesoderm / physiology
  • Myoblasts, Cardiac / cytology
  • Myoblasts, Cardiac / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Organogenesis / genetics*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • APLN protein, Xenopus
  • APLNR protein, Xenopus
  • Apelin Receptors
  • Chemokines
  • Intercellular Signaling Peptides and Proteins
  • Receptors, G-Protein-Coupled
  • Xenopus Proteins
  • Zebrafish Proteins
  • apelin receptor, zebrafish
  • apln protein, zebrafish